The role of solvent in mechanochemical and sonochemical cocrystal formation: a solubility-based approach for predicting cocrystallisation outcome
The role of solvent in mechanochemical and sonochemical cocrystal formation: a solubility-based approach for predicting cocrystallisation outcome
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DOI：
10.1039/b815174a
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发表时间：
2009-01-01
期刊：
影响因子：
3.1
通讯作者：
Jones, William
中科院分区：
文献类型：
--
作者：
Friscic, Tomislav;Childs, Scott L.;Jones, William
机械化学液体辅助研磨（LAG）和声化学（SonicSlurry）技术进行了比较，作为方法来构建四个模型药物共晶涉及茶碱和咖啡因作为药物成分和L-苹果酸或L-酒石酸作为药物共晶形成剂。对于这些模型系统，使用参数eta（溶剂体积与样品重量之比）解释结果。在四种不同的溶剂中使用LAG在eta = 0.25和10 μ L mg（-1）下研究四种共晶，以及在eta = 2、6和12 μ L mg（-1）下进行SonicSlurry实验。当eta = 0.25 μ L mg（-1）时，在所有标准LAG实验中观察到共晶的形成。仅观察到茶碱和L-苹果酸的共晶体通过纯研磨（即不添加液体）形成共晶体。在非常低的h值（低于0.5 μ L mg（-1））下的LAG实验表明，共晶形成的速率取决于液体的选择，并随h的增加而增加。SonicSlurry实验在2、6和12 μ L mg（-1）的较高eta值下进行，提供了三种不同的结果：纯共晶、共晶与共晶组分的混合物或单一共晶组分。在eta = 10 μ L mg（-1）下的LAG实验产生与在eta = 12 μ L mg（-1）下的SonicSlurry实验一致的结果。测量近似的溶解度的个别共晶组分显示，产品的形成是不受特定的加工方法，但由反应物的饱和度。基于共晶组分的近似溶解度的实验方法已经被开发用于定性地预测在不同h值下的共晶实验的结果。作为一般准则，在所有共晶组分保持饱和的条件下预期共晶形成。
Mechanochemical liquid-assisted grinding (LAG) and sonochemical (SonicSlurry) techniques have been compared as methods to construct four model pharmaceutical cocrystals involving theophylline and caffeine as pharmaceutical ingredients and L-malic or L-tartaric acid as pharmaceutical cocrystal formers. For these model systems, the results are interpreted using the parameter eta, the ratio of solvent volume to sample weight. Each if the four cocrystals was studied in four different solvents using LAG at eta = 0.25 and 10 mu L mg(-1), as well as SonicSlurry experiments at eta = 2, 6 and 12 mu L mg(-1). The formation of the cocrystal is observed in all standard LAG experiments when eta = 0.25 mu L mg(-1). Cocrystal formation by neat grinding, i.e. with no liquid added, was observed only for the cocrystal of theophylline and L-malic acid. LAG experiments at very low h values (below 0.5 mu L mg(-1)) revealed that the rate of cocrystal formation depended on the choice of the liquid and increases with h. SonicSlurry experiments performed at higher eta values of 2, 6 and 12 mu L mg(-1) provided three different outcomes: the pure cocrystal, a mixture of the cocrystal with a cocrystal component, or a single cocrystal component. LAG experiments at eta = 10 mu L mg(-1) produced results consistent with the SonicSlurry experiments at eta = 12 mu L mg(-1). Measuring approximate solubilities of individual cocrystal components revealed that product formation is not dictated by the specific processing method but by saturation levels of reactants. An experimental approach based on approximate solubilities of cocrystal components has been developed to qualitatively predict the outcome of cocrystallization experiments at different h values. As a general guideline, cocrystal formation is expected under conditions in which all cocrystal components remain saturated.